Project Abstract Millions of people are exposed to smoke emissions from wildfires in the United States (U.S.). Increasing evidence from population-based studies indicates that acute exposure to wildland fire (WF) smoke induces acute respiratory effects. Observations made in these studies are inconclusive about the cardiovascular effects of WF smoke. However, these studies are limited by a relatively higher potential for exposure misclassification and their inherent weakness to detect small population level differences. Additionally, longer-term effects of cumulative exposure, such as experienced by wildland firefighters, are currently unknown. Furthermore, health studies among firefighters have been limited to acute pulmonary responses and non-specific systemic end-points, although cardiovascular events cause the largest number of on-the-job deaths among wildland firefighters. The proposed study is designed to address NIOSH?s ?Public Safety? sector and ?Cancer, Reproductive, and Cardiovascular Diseases? cross-sector by assessing the association between occupational exposure to WF smoke and precursors of cardiovascular disease. The hypothesis of the proposed study is that WF smoke exposure induces adverse cardiovascular effects among WFFs as indicated by lipid dysregulation, and changes in vascular structure and function. Specifically we will determine the effect of occupational exposure to WF smoke on (1) traditional and novel CVD lipid risk factors and (2) measures of vascular structure and atherosclerotic progression. Baseline and prospective changes in these measures will be compared between wildland firefighters and a control non-exposed group of emergency medical technicians (EMTs). The use of disease precursors as outcomes will enable findings that are relevant for characterizing risks that may evolve while still working and those that could develop after retirement. The objective of the proposed study is well aligned with NIOSH?s priority extramural research goal to ?reduce the incidence of chronic and acute diseases in firefighters that may be related to ? combustion products,? by conducting a study using precursors of disease as outcomes. This work will contribute to the development of relevant early disease detection. Overall, following the successful completion of the proposed study we expect to have determined the contribution of occupational WF smoke exposure to CVD development. The envisaged outputs from the proposed research, which would include publicly accessible results and publications, would directly inform NIOSH?s priority goal to reduce incidence of exposure and illnesses among wildland firefighters. These outputs will contribute to appropriate risk assessment of WF smoke exposure, the development of exposure and risk mitigation strategies, and methods to test their effectiveness. Finally, the study results will be disseminated and made accessible to its immediate audience, the wildland firefighting community. Accessibility will also be enhanced by targeting study results for open access publication.